Download VIRUS STRUCTURE

VIRUS STRUCTURE AND
CLASSIFICATION
Claude MUVUNYI M.D., Ph.D.
Terminology
In 1962, Caspar et al. defined the following terms:
 Virion: The complete infectious virus particle.
 Capsid: The protein coat that surrounds nucleic acid.
 Nucleocapsid: The nucleic acid plus the capsid.
 The nucleocapsid may be enclosed inside an ENVELOPE containing
proteins encoded by the virus.
 STRUCTURE UNITS are the smallest equivalent building units of the
capsid.
 Capsomeres: The structural protein units that made up the capsid.
General structure of viruses
 Viruses composed of nucleic acid either DNA or RNA,
surrounded by a protein coat called the capsid.
 The capsid is composed of small structural units called
capsomeres.
 The capsid protects nucleic acid from inactivation by
the outer physical conditions.
 Some viruses have additional lipoprotein envelope ,
composed of virally coded protein and host lipid. The
viral envelope is covered with glycoprotein spikes.
General structure of viruses
 Some viruses have enzymes inside the virion. All ss- RNA
viruses with negative polarity have the enzyme transcriptase (
RNA dependent RNA polymerase) inside virions.
Virus Shapes
General morphology
Viruses may be classified into several morphological
types on the basis of their capsid architecture as revealed
by electron microscopy and a technique called x-ray
crystallography.
Virus structure
• Self assembly of virus capsids follows two basic patterns:
– Helical symmetry, in which
the protein subunits and the nucleic
acid are arranged in a helix.
– Icosahedral symmetry, in which
the protein subunits assemble into
a symmetric shell that covers the
nucleic acid-containing core.
Virus structure
• Larger viruses often have a complex
architecture
consisting of both helical and isometric
symmetries
confined to different structural components.
• Small viruses, e.g., hepatitis B virus or the
members of the picornavirus or parvovirus
family, are orders of magnitude more resistant
than are the larger complex viruses, e.g.
members of the herpes or retrovirus families.
Basic virus structure
DNA
or
+
Capsid
protein
Nucleocapsid
=
Naked
capsid virus
RNA
Nucleocapsid
+
Lipid membrane,
glycoproteins
Enveloped virus
Capsid symmetry
Icosahedral
Helical
Naked capsid
Enveloped
Matrix
Lipid
Glycoprotein
http://www.ncbi.nlm.nih.gov/ICTVdb/Images/Ackerman/Animalvi/Adenovir/799-16.htm
Adenovirus
Electron micrograph
Foot and mouth disease virus
Crystallographic model
http://virology.wisc.edu/virusworld/ICTV8/fmd-foot-and-mouth-ictv8.jpg
Icosahedral naked capsid viruses
Helical naked capsid viruses
Protein
Caspar and Klug, Adv Virus Res. 1960;7:225-325
http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/em_tmv.gif
RNA
Tobacco mosaic virus
Electron micrograph
Tobacco mosaic virus
Model
http://virology.wisc.edu/virusworld/images/herpescapsid.GIF
http://web.uct.ac.za/depts/mmi/stannard/emimages.html
Icosahedral enveloped viruses
Herpes simplex virus
Electron micrograph
Herpes simplex virus
Nucleocapsid cryoEM model
http://web.uct.ac.za/depts/mmi/stannard/paramyx.html
http://web.uct.ac.za/depts/mmi/stannard/fluvirus.html
Helical enveloped viruses
Influneza A virus
Electron micrograph
Paramyxovirus
Electron micrograph
Properties of enveloped viruses
• Envelope is sensitive to
–
–
–
–
Drying
Heat
Detergents
Acid
• Consequences
–
–
–
–
–
Must stay wet during transmission
Transmission in large droplets and secretions
Cannot survive in the gastrointestinal tract
Do not need to kill cells in order to spread
May require both a humoral and a cellular immune
response
Adapted from Murray, P.R. Rosenthal K.S., Pfaller, M.A. (2005) Medical Microbiology, 5th edition, Elsevier Mosby, Philadelphia, PA Box 6-5
Properties of naked capsid viruses
• Capsid is resistant to
–
–
–
–
–
Drying
Heat
Detergents
Acids
Proteases
• Consequences
–
–
–
–
–
–
Can survive in the gastrointestinal tract
Retain infectivity on drying
Survive well on environmental surfaces
Spread easily via fomites
Must kill host cells for release of mature virus particles
Humoral antibody response may be sufficient to neutralize infection
Adapted from Murray, P.R. Rosenthal K.S., Pfaller, M.A. (2005) Medical Microbiology, 5th edition, Elsevier Mosby, Philadelphia, PA , Box 6-4
FIVE BASIC STRUCTURAL FORMS OF
VIRUSES IN NATURE
 Naked icosahedral e.g. poliovirus, adenovirus, hepatitis A virus
 Naked helical e.g. tobacco mosaic virus. So far no human viruses with
this structure are known
 Enveloped icosahedral e.g. herpes virus, yellow fever virus, rubella
virus
 Enveloped helical e.g. rabies virus, influenza virus, parainfluenza virus,
mumps virus, measles virus
 Complex e.g. poxvirus
CLASSIFICATION OF VIRUS
Naming of Viruses
Usually based on data available when a virus is
discovered:
 Diseases viruses are associated with, e.g.: Poxvirus, Hepatitis virus,
HIV, Measles virus.
 Cytopathology occuring during infection, e.g.: Respiratory Syncytial
virus, Cytomegalovirus.
 Site of infection, e.g.: Adenovirus, Enterovirus, Rhinovirus,
Enterovirus.
 Places where viruses were found or people who discovered them,
e.g.: Epstein-Barr virus, Rous Sarcoma, Rift Valley Fever.
 Biochemical features, e.g.: Retrovirus, Picornavirus
Such names are not useful for orderly classification!!!!
These naming conventions can lead to confusion
later e.g.: viral hepatitis is caused by at least 6 different
viruses
“Infectious”
Viral
hepatitis
“Serum”
A
E
F, G,
? Other *
NANB
B
Enterically
transmitted
C
Parenterally
transmitted
D
* 10-20% of cases of presumed viral hepatitis are still
not accounted for.
Related Herpesviruses Cause Many Different
Diseases
• HSV
•
•
•
•
Herpes Simplex Virus Cold sores (type 1),
Genital lesions (type 2)
VZV Varicella Zoster Virus Chicken pox
CMV Cytomegalovirus
Mononucleosis
EBV Epstein-Barr Virus
Mononucleosis,
Burkitt’s lymphoma,
Nasopharyngeal
carcinoma
• and HHV-6, HHV-7, HHV-8….. (Human HerpesVirus-#)
Therefore if these viruses were classified based on their
symptoms their relationships would be missed.
Thus,
Different viruses can cause (nearly) the same symptoms.
e.g., the hepatitis viruses
However, different members of the same group can cause
different symptoms. e.g., the herpes viruses
So virologists had to devise more orderly
schemes for classification
Meeting Classification Needs
• A universal system of viral classification and a unified
taxonomy was established by the International
Committee on Taxonomy of Viruses (ICTV) in
1966. The system makes use of a series of ranked
taxons, with the:
• - Order (-virales) being the highest currently recognized.
•
- then Family (-viridae)
•
- Subfamily (-virinae)
•
- Genus (-virus)
•
- Species ( eg: tobacco mosaic virus)
By the year 2000, over 4000 viruses of plants, animals and
bacteria had been included in 71 families, 9 subfamilies
and 164 genera.
The ICTV seeks input from a wide range of
virologists and meets every three years to
revise the taxon.
ICTV Classification Uses a Hierarchical Scheme
The most important characters are at the top of the Scheme.
Other characters are ranked below in order of importance.
(Suffix:
viridae)
This scheme brings order to the
classification of viruses irrespective
(Suffix:
of their hosts or disease symptoms
virinae)
(Suffix:
virus)
Poxviridae
Herpesviridae
Retroviridae
Picornaviridae
Primary characteristics used in
classification
Viruses are classified according to the nature of their genome and
their structure
Genetic material Is Most Important!!!
 form of nucleic acid
• ssDNA (+ or - strand)
• dsDNA
• ssRNA (+ or - strand)
• dsRNA
• segmented RNA
 genetic organization
 sequence homology

• DNA sequence
•
• Hybridization
 Morphology: by electron microscopy
Secondary characteristics
Replication strategy
 Sometimes a group of viruses that seems to be a
single group by the above criteria is found to
contain a subgroup of viruses which have a
fundamentally different replication strategy –
 In this case the group will be divided based on
the mode of replication.
David Baltimore’s viral genome classification scheme
Genomes and strategies of replication most important features for classification.
Baltimore originally proposed six different major categories:
Class I: Viruses with double strand DNA genomes. (Adenoviruses)
Class II: Viruses with single strand DNA genomes. (Geminiviruses)
Class III: Viruses with double strand RNA genomes. (Reoviruses)
Class IV: Plus-sense RNA Viruses.
(Picornaviruses)
Class V: Viruses with
Negative strand RNA
genomes. (Rhabdoviruses)
Class VI: Viruses with
Reverse transcribed RNA genomes.
(Retroviruses)
We can now add a Seventh Genome
Class.
Class VII: DNA Genomes replicated by
reverse transcription. (Hepatitis B
like Pararetroviruses)
RNA Virus Families
Several general features are evident from the classification:
 None of the dsRNA viruses are enveloped.
 The minus-strand viruses are enveloped with helical nucleocapsids.
 Most of the plus-strand strand viruses have icosahedral nucleocapsids.
 Plus strand viruses vary in having envelopes.
 Most of the plus strand viruses have a single genomic RNA.
DNA Viruses
DNA Viruses differ in many features from RNA Viruses:
Only three families are enveloped.
All families except for the poxviruses replicate in nuclei.
Many families have very complex nucleocapsids.